DIABETES

MELLITUS
Definition, Presentation,
Diagnosis, and
Classification

Diabetes Mellitus
A

metabolic disorder of multiple aetiology

characterized by chronic hyperglycaemia with
disturbances of carbohydrate, fat and protein
metabolism resulting from defects in insulin secretion,
insulin action or both

Associated with a risk of developing late diabetic

complications including
Microvascular (retinopathy, nephropathy)
Macrovascular (atherosclerosis)
Neuropathy
2

Diabetes : A malignant vascular disorder

the most frequent cause
of new cases of
blindness among adults
aged
20 to 74.

Stroke
2-4 x risk for stroke
and coronary heart
disease *)

Diabetic
Retinopathy
Cardiovascular
disease

Diabetic
Nephropathy
Accounts for ~40% of all new cases of
end-stage renal disease (ESRD).
Most common cause of
renal failure Dialysis

Myocardiac infarct
Diabetic
Neuropathy

*) Most common
cause of death in
diabetics

Most common cause of

lower limb amputation

National Diabetes Information Clearinghouse. Diabetes StatisticsComplications of Diabetes.

http://www.niddk.nih.gov/health/diabetes/pubs/dmstats/dmstats.htm#comp.

Diabetes is an increasing healthcare epidemic

throughout the world
IDF Regions and global projections for the number of people with
diabetes (20-79 years), 2010-2030

Africa
Middle East and
North Africa

55.2
66.2
+20
%

37.4
53.2
+42
%

Europe

26.5
51.7
+94
%

North America
South and Central America
South-East Asia
Western Pacific

IDF. Diabetes Atlas 4th Edition 2009

16.0
29.6
+65%

12.1
23.9
+98
%

58.7
101.
0
+72
%

Worldwide:
284.6 million people in 2010
438.4 million projected for 2030
54% increase

76.7
112.
8
+47
%

Number of
people with
diabetes by age
group,
2010 and 2030

IDF Diabetes Atlas, 4th ed. 2009

Top 10
Number of people with diabetes
(20-79 years), 2010 and 2030

IDF Diabetes Atlas, 4th ed. 200

Prediabetes
Indonesian
Indonesian basic
basic
health
health research
research
(Riskesdas)
(Riskesdas)
Diagnosed
Diagnosed DM
DM =
=
1,5%
1,5%
Undiagnosed
Undiagnosed DM
DM =
=
4,2%
4,2%
Total
Total DM
DM =
= 5,7%
5,7%
IGT
IGT =
= 10,2
10,2 %
%

People who
who know
know
People
they have
have diabetes
diabetes
they

People who
who dont
dont
People
know they
they have
have
know
diabetes
diabetes

Prevalensi DM
4

3
1
2

Jawa Timur 6,8%

Tertinggi :
1. Kalimantan Barat 11,1%
2. Maluku
11,1%
3. Riau
10,4%
4. NAD
8,5%

Terendah :
Papua 1,7%
NTT 1,8%

INSULIN &
HOMEOSTASIS GLUKOSA

PANKREAS

Insulin
production and
action

Siapa saja yang bisa terkena

DM ?
1. Usia 45 tahun
2. Usia < 45 tahun, terutama dengan kegemukan, yang disertai dengan
faktor resiko :
kebiasaan tidak aktif
turunan pertama dari orang tua dengan DM
riwayat melahirkan bayi dengan BB lahir bayi > 4000 gram, atau
riwayat DM gestasional
hipertensi ( 140/90 mmHg)
kolesterol HDL 35 mg/dL dan atau trigliserida 250 mg/dL
menderita polycystic ovarial syndrome (PCOs) atau keadaan lain
yang terkait dengan resistensi insulin
adanya riwayat toleransi glukosa terganggu (TGT) atau glukosa
darah puasa terganggu (GDPT) sebelumnya Prediabetes
memiliki riwayat penyakit jantung

NORMAL

PREDIABETES

DIABETES

Puasa
Puasa :: <100
<100 mg/dl
mg/dl

IFG
IFG :: 100-125
100-125 mg/dl
mg/dl

>126
>126 mg/dl
mg/dl

22 jam
jam PP:
PP: <140
<140 mg/dl
mg/dl

IGT
IGT :: 140-199
140-199 mg/dl
mg/dl

>200
>200 mg/dl
mg/dl

FPG : Fasting plasma glucose (Gula darah puasa)

2-h PG : 2-hour plasma glucose
(Gula darah 2 jam setelah makan)
IFG : Impaired fasting glucose (Gula darah puasa terganggu)
IGT : Impaired glucose tolerance
(Toleransi glukosa terganggu)

Bagaimana diagnosis DM ditegakkan ?

Gejala klasik DM + GDA 200 mg/dL
atau
2.
Gejala klasik DM
+
GDP 126 mg/dL dengan puasa 8 jam
atau
1.

3.

2 jam PP TTGO 200 mg/dL

TTGO dengan beban 75 g glukosa

Keluhan klasik DM : rasa haus yang berlebihan, sering kencing

terutama malam hari dan berat badan menurun dengan cepat.
Keluhan lain dapat berupa lemah badan, kesemutan, gatal, mata kabur,
gairah seks menurun, luka sukar sembuh.

Type 2 Diabetes:
Progression from Underlying Defects
Insulin
Sensitivity

Insulin
Secretion

Macrovascular
Diseases

30%

50%

Type 2
Diabetes

50%

50%

70%-100%

IGT

40%

70%

150%

Impaired
Glucose
Metabolism

10%

100%

100%

Normal Glucose Metabolism

Adapted from Groop.Diabetes Obesity Metab 1999;1(Suppl.1):S1-S7.

The progressive nature of type 2 diabetes

Normal

Impaired
glucose
tolerance

Type 2
diabetes

Insulin
sensitive

Late type 2
diabetes
complications
Hyperglycaemia

Normal
insulin
secretion

Insulin
resistance
-cell
exhaustion

Normoglycaemia

Insulin resistance

Fasting plasma glucose

Insulin sensitivity
Insulin secretion

Adapted from Bailey CJ et al. Int J Clin Pract 2004; 58:867876.

Groop LC. Diabetes Obes Metab 1999; 1 (Suppl. 1):S1S7.

KLASIFIKASI DM
Tipe 1

Destruksi sel beta, umumnya menjurus ke defisiensi

insulin absolut
Autoimun
Idiopatik

Tipe 2

Bervariasi mulai yang terutama dominan resistensi

insulin disertai defisiensi insulin relatif sampai yang
terutama defek sekresi insulin disertai resistensi
insulin

Tipe lain

Defek genetik fungsi sel beta

Defek genetik kerja insulin
Penyakit eksokrin pankreas
Endokrinopati
Karena obat atau zat kimia
Infeksi
Sebab imunologi yang jarang
Sindrom genetik lain yang berkaitan dengan DM

Diabetes mellitus gestasional

GLYCEMIC GOALS IN ADULT

IDF

AACE

ADA

HbA1C (%)

< 6.5

6.5

< 7.0

Fasting/preprandial glucose
(mmol/L / mg/dL)

< 6.0 / < 110

< 6.0 / < 110

3.9-7.2 / 70-130

2-h postprandial glucose

(mmol/L / mg/dL)

< 7.8 / < 140

< 7.8 / < 140

< 10.0 / < 180*

ADA recommends that postprandial glucose measurements should be made 12h after the beginning of the meal
IDF : International Diabetes Federation
AACE : American Association of Clinical Endocrinologist

Diabetes Mellitus Management

2. Exercise

1. Diet
3. BW
Management

4. drugs : Pills /
Insulin

5. Routinely
Control

Dosing, efficacy and cost of oral agents for

treatment of type 2 diabetes mellitus
patients
Doses (mg)

Maximum
dose (mg)

Maximum
effective
dose (mg)

HbA1c
reduction
(%)

Cost/year
($)

Glyburide

1.25, 2.5, 5

10 bid

10 qd

1.5 - 2.0

130

Glipizide

5, 10

20 bid

10 qd-bid

1.5 2.0

175

2.5, 5, 10

20 qd

5 20qd

1.5 2.0

300

Glimepiride

1, 2, 4

8 qd

4 qd

1.5 2.0

330

Repaglinide

0.5, 1, 2

4 tid

2 tid

1.5 2.0

910

Neteglinide

60, 120

120 tid

120 tid

0.5 1.0

1.100

Metformin*

500, 850, 1000

850 tid

1000 bid

1.5 2.0

600

Glucophage-XR*

500

2000 qd

2000 qd

1.5 2.0

1.000

Rosiglitazone

4, 8

8 qd, 4 bid

4 bid

1.5

1.875

15, 30, 45

45 qd

45 qd

1.5

2.110

50, 100

100 tid

50 tid

0.5 1.0

700

25, 50, 100

100 tid

100 tid

0.75 1.2

880

Glucovance*

1.25/250, 2.5/500, 5/500

5/500, 2 bid

2.5/500, 2 bid

1.3

1.400

Avandamet*

1/500, 2/500, 4/500

2/500, 2 bid

2/500, 2 bid

N/A

2.170

2.5/250, 2.5/500, 5/500

5/500, 2 bid

5/500, 2 bid

2.1

1.400

Agent

Glipizide-GITS*

Pioglitazone
Acarbose
Miglitol

Metaglip*

Incretin mimetic / DPP IV

Sheehan MT. Clinical Medicine & Research 2003; 1 (3): 189-200

The New Paradigm of (Type 2)

Diabetes Treatment

Treatment Driven by Target (A1C<7%)

Early Combinations (including with insulin)
Aggressive Insulin Treatment

Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]

(Adapted with permission from: Ismail-Beigi F, et al. Ann Intern Med 2011;154:554)

Diabetes Care, Diabetologia. 19 April 2012

[Epub ahead of print]

Diabetes Care, Diabetologia. 19 April 2012

[Epub ahead of print]

Diabetes Care, Diabetologia.

19 April 2012 [Epub ahead of print]

Type-2
Type-2 DM
DM management
management
DIiagnosis

STEP-1
GHS
Oral monotherapy

STEP-2

GHS
2 combo-therapy

3 combo-therapy

Perkeni, 2011
Perkeni, 2011

STEP-3

GHS
2 combo-therapy
+
Basal insulin

GHS
Intensive Insulin
Basal plus
Basal bolus

ADA-EASD Position Statement: Management of

Hyperglycemia in T2DM

OTHER CONSIDERATIONS
Comorbidities
-Coronary Disease
-Heart Failure
-Renal disease

Metformin
Metformin :: May
May use
use unless
unless
condition
condition is
is unstable
unstable or
or severe
severe

Avoid
Avoid TZDs
TZDs

?? Effects
Effects of
of incretin-based
incretin-based
therapies
therapies

-Liver dysfunction
-Hypoglycemia

Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]

ADA-EASD Position Statement: Management of

Hyperglycemia in T2DM

OTHER CONSIDERATIONS
Comorbidities
-Coronary Disease
-Heart Failure
-Renal disease
-Liver dysfunction
-Hypoglycemia

Increased
Increased risk
risk of
of hypoglycemia
hypoglycemia

Metformin
Metformin &
& lactic
lactic acidosis
acidosis
US:
US: stop
stop @SCr
@SCr 1.5
1.5 (1.4
(1.4

women)
women)
UK:
UK: dose
dose @GFR
@GFR <45
<45 &
& stop
stop
@GFR
@GFR <30
<30

Caution
Caution with
with SUs
SUs (esp.
(esp. glyburide)
glyburide)

DPP-4-is
DPP-4-is dose
dose adjust
adjust for
for most
most

Avoid
Avoid exenatide
exenatide ifif GFR
GFR <30
<30

Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]

ADA-EASD Position Statement: Management of

Hyperglycemia in T2DM

OTHER CONSIDERATIONS
Comorbidities
-Coronary Disease
-Heart Failure
-Renal disease

Most
Most drugs
drugs not
not tested
tested in
in advanced
advanced

liver
liver disease
disease

Pioglitazone
Pioglitazone may
may help
help steatosis
steatosis

Insulin
Insulin best
best option
option ifif disease
disease
severe
severe

-Liver dysfunction
-Hypoglycemia

Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of

print]

ADA-EASD Position Statement: Management of

Hyperglycemia in T2DM

OTHER CONSIDERATIONS
Comorbidities
-Coronary Disease
-Heart Failure
-Renal disease
-Liver dysfunction
-Hypoglycemia

Emerging
concerns
Emerging
concerns
regarding
regarding association
association with
with
increased
increased mortality
mortality

Proper
Proper drug
drug selection
selection in
in
the
hypoglycemia
the
hypoglycemia
prone
prone

Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]

Thank You